This work represents a continuation of the concept that changes in the peripheral metabolism of amino acids, particularly the neutral amino acids and specifically the aromatic amino acid precursors of the neurotransmitters norepinephrine, octopamine, other beta-hydroxyphenylethylamines, dopamine and serotonin, are causally related to the etiology of hepatic encephalopathy. In these studies we have utilized animal models of hepatic encephalopathy following end to side portocaval shunt, particularly measuring changes in the brain uptake index of the neutral amino acids across the blood brain barrier. More recent work has utilized pure isolated capillary preparations in both animals with both end-to-side portocaval shunts, as well as normal animals. Since the blood-brain barrier appears to reside in the capillaries such changes as may be seen in the blood-brain barrier have been detected in such isolated capillary preparations. Such work also implicates ammonia, its synthesis to glutamine and exchange of glutamine for neutral amino acids across the blood-brain barrier.